A Possible Role of Skeletal Muscle‐Derived Adiponectin in the Regulation of Skeletal Muscle Mass

Abstract

Aging‐associated severe skeletal muscle atrophy, so‐called sarcopenia, is considered as a risk factor for falls in older adults. Recent cohort studies shows high circulating adiponectin levels predict decreased muscle strength among older adults. Adiponectin, one of adipokines, is exclusively synthesized in adipocytes, is secreted into circulation, binds to adiponectin receptors (AdRs), especially AdR1, and exhibits insulin‐sensitizing effects to stimulate the utilization of glucose and lipids in skeletal muscle cells. We hypothesize that high adiponectin levels may have atrophic effects on skeletal muscle cells. Therefore, this study investigated aging‐associated changes in adiponectin expression in skeletal muscle and effects of high adiponectin levels on myogenic differentiation. All procedures for animal experiments were carried out in accordance with the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the National Institutes of Health (Bethesda, MD, USA) and were approved by the Animal Use Committee of Toyohashi SOZO University. Aging‐associated up‐regulation of adiponectin in fast extensor digitorum longus muscle was observed. Agonist for AdRs, AdipoRon, suppressed myogenic differentiation of C2C12 cells in a dose‐dependent manner. Knockdown of AdR1 in C2C12 myoblasts induced by small interfering RNA (siRNA), partially depressed the AdipoRon‐induced suppression of C2C12 differentiation. Aging‐associated up‐regulation of adiponectin in skeletal muscle may induced muscle atrophy in especially fast skeletal muscle.Support or Funding InformationThis study was supported, in part, by Grants‐in‐Aid for challenging Exploratory Research (26560372), and Grants‐in‐Aid for Scientific Research (C, 26350818) from the Japan Society for the Promotion of Science, the Uehara Memorial Foundation, the Naito Foundation, Graduate School of Health Sciences, Toyohashi SOZO University, Descente Sports Foundation, and All Japan Coffee Association. No COI.